Project Summary and Abstract The standard paradigm for the detection of HIV-associated CNS impairment (HIVCI) involves protocols that require trained personnel, often impractical and unavailable in typical outpatient clinical settings. As a result, HIVCI is often undetected or detected late, leading to a lower quality of life and decreased survival. With the need for earlier detection and the availability of new medical billing codes, a recent push to change the paradigm towards earlier screening of cognitive impairment as a precursor to diagnostic testing is currently underway; however, severely limited in its capability and scope. Therefore, there is an urgent need to enable this new paradigm to detect HIVCI earlier in the disease course (a topic area of interest to NIMH?s Division of AIDS Research and HIV Neuropathogenesis Program): universal screening (not requiring trained staff) to reliably refer HIV+ patients to neuropsychometric (NP) diagnostic testing (by trained staff). This SBIR proposes a novel value proposition: A universal screening tool based on a known functional impairment - driving. Thus, the long-term goal of this SBIR is a new Virtual Driving and CNS Assessment System (VDCA) as a valid, low cost, easy-to-administer, universal screening system for HIV+ patients. To achieve these objectives and develop the VDCA, we will leverage (1) our commercially-successful virtual driving test (VDT) as a platform on which to develop the VDCA; (2) our team?s scientific know-how in utilizing driving to task cognitive, sensorimotor and memory systems (including those implicated in HIVCI); and (3) our exclusive access to an established longitudinal cohort of HIV+ participants. Our preliminary work using magnetoencephalography (MEG) supports the development of the VDCA as a meaningful probe of cognitive control and functional capacity that will become a universal screen for HIVCI. We propose three Phase 1 aims before pursuing a larger Phase II project: Aim 1: Develop a research production-grade version of VDCA incorporating new driving scenarios to task cognitive, sensorimotor and memory systems with associated metrics as guided by our complementary work with MEG; Aim 2: Conduct an observational pilot study by recruiting HIV+ patients from Drexel University?s established and NIMH-supported longitudinal cohort to test the hypothesis that VDCA performance can differentiate participants with and without HIVCI - thereby providing initial evidence to support the VDCA as a HIVCI screening solution; Aim 3: Assess the usability, feasibility and barriers of implementing the VDCA in a clinical setting by leveraging insights from the Aim 2 implementation team and from a comprehensive healthcare team providing HIV healthcare services in a limited-resource clinical setting. These insights will provide support for utility and feasibility of the VDCA as a universal screen and set the direction for future refinement, testing and evaluation in Phase II.